Publications by authors named "Grace Teng"

Article Synopsis
  • The study investigates the roles of all four mammalian Argonaute (AGO) proteins in microRNA (miRNA) activity and finds that only AGO2 is essential for miRNA function, while AGO1, AGO3, and AGO4 can be disregarded for this purpose.
  • Instead of miRNA regulation, AGO1, AGO3, and AGO4 are shown to influence type 2 immunity through their role in splicing precursor mRNA in CD4 T helper lymphocytes.
  • The research highlights a direct interaction between nuclear AGO3 and SF3B3, which is part of the splicing machinery, affecting mRNA splicing and specifically the Nisch gene isoforms, implicating
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Many therapeutics for cardiomyopathy treat the symptoms of the disease rather than the underlying mechanism. The mechanism of cardiomyopathy onset is believed to include two means: calcium sensitivity changes and myosin activity alteration. Trifluoperazine is a compound that binds troponin, and other components of the calcium pathway, which impacts calcium regulation of contraction.

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  • Exacerbations of asthma symptoms are a major concern, linked to bacterial imbalances and infections that can worsen the condition.
  • Research shows that bacterial lipopolysaccharide (LPS) triggers production of oncostatin M (OSM), which is associated with severe asthma and inflammation.
  • The study suggests that targeting OSM could be a potential strategy to prevent worsening asthma symptoms linked to bacterial factors.
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  • Compromised lung epithelial cells can become senescent, leading to fibrosis, with unclear origins and identities of these cells in diseases like idiopathic pulmonary fibrosis (IPF).
  • The research found the senescence marker p16 predominantly in damaged epithelial areas of IPF and systemic sclerosis-associated interstitial lung disease (SSc-ILD), alongside basal epithelial markers Keratin 5 and Keratin 17.
  • Using in vitro models and single-cell RNA sequencing, the study identified a specific population of basal epithelial cells enriched for senescence markers, revealing insights into their gene expression and suggesting potential markers for future research on lung diseases.
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Mutations in the α-cardiac actin ACTC1 gene cause dilated or hypertrophic cardiomyopathy. These diseases are the result of changes in protein interactions between ACTC protein and force-generating β-myosin or the calcium-dependent cardiac-tropomyosin (cTm) and cardiac troponin (cTn) regulatory complex, altering the overall contractile force. The T126I and S271F ACTC variants possess amino acid substitutions on the other side of actin relative to the myosin or regulatory protein binding sites on what we call the "dark side" of actin.

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Hypertrophic cardiomyopathy is a commonly occurring cardiovascular disease resulting primarily from changes in proteins participating in muscle contraction in the heart, including the cardiac actin protein. Changes in cardiac actin located exclusively in the myosin binding site are called M-class variants and include the H88Y, R95C, and E99K substitutions and F90Δ deletion. The prevailing hypothesis for these mutations is that hypertrophic cardiomyopathy is the result of increased calcium sensitivity of contraction in the myocardium.

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The RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci. RAG2 localizes directly to lysine 4 trimethylated histone 3 (H3K4me3) through a plant homeodomain (PHD) finger. The relative contribution of RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known.

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The modular, noncontiguous architecture of the antigen receptor genes necessitates their assembly through V(D)J recombination. This program of DNA breakage and rejoining occurs during early lymphocyte development, and depends on the RAG1 and RAG2 proteins, whose collaborative endonuclease activity targets specific DNA motifs enriched in the antigen receptor loci. This essential gene shuffling reaction requires lymphocytes to traverse several developmental stages wherein DNA breakage is tolerated, while minimizing the expense to overall genome integrity.

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B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2 recombinase. However, the RAG proteins bind widely to open chromatin, which suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here we show that developmental downregulation of interleukin 7 (IL-7)-receptor signaling in small pre-B cells induced expression of the bromodomain-family member BRWD1, which was recruited to a specific epigenetic landscape at Igk dictated by pre-B cell receptor (pre-BCR)-dependent Erk activation.

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The RAG1 endonuclease, together with its cofactor RAG2, is essential for V(D)J recombination but is a potent threat to genome stability. The sources of RAG1 mis-targeting and the mechanisms that have evolved to suppress it are poorly understood. Here, we report that RAG1 associates with chromatin at thousands of active promoters and enhancers in the genome of developing lymphocytes.

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Purpose: Although it has been revealed clinically that double-jaw orthognathic surgery induces a systemic increase in the baseline bone turnover and subsequently accelerates postoperative orthodontic tooth alignment, it is not clear whether less extensive osteotomy, such as interdental osteotomy, would be intensive enough to accelerate postoperative orthodontic tooth alignment.

Materials And Methods: Twelve adult male beagle dogs were randomly assigned to 2 groups. The sham control group (n = 6) received orthodontic tooth alignment of the maxillary incisors, and the experimental group (n = 6) received orthodontic tooth alignment of the maxillary incisors and interdental osteotomies between the maxillary third incisor and canine on both sides concurrent with the beginning of orthodontic tooth alignment.

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Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4(-)CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations.

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Although most genes are expressed biallelically, a number of key genomic sites--including immune and olfactory receptor regions--are controlled monoallelically in a stochastic manner, with some cells expressing the maternal allele and others the paternal allele in the target tissue. Very little is known about how this phenomenon is regulated and programmed during development. Here, using mouse immunoglobulin-κ (Igκ) as a model system, we demonstrate that although individual haematopoietic stem cells are characterized by allelic plasticity, early lymphoid lineage cells become committed to the choice of a single allele, and this decision is then stably maintained in a clonal manner that predetermines monoallelic rearrangement in B cells.

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Cohesin enables post-replicative DNA repair and chromosome segregation by holding sister chromatids together from the time of DNA replication in S phase until mitosis. There is growing evidence that cohesin also forms long-range chromosomal cis-interactions and may regulate gene expression in association with CTCF, mediator or tissue-specific transcription factors. Human cohesinopathies such as Cornelia de Lange syndrome are thought to result from impaired non-canonical cohesin functions, but a clear distinction between the cell-division-related and cell-division-independent functions of cohesion--as exemplified in Drosophila--has not been demonstrated in vertebrate systems.

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Noncoding RNAs (ncRNAs), both small and large, have recently risen to prominence as surprisingly versatile regulators of gene expression. In fact, eukaryotic transcriptomes are rife with RNAs that do not code for protein, though the majority of these species remains wholly uncharacterized. The functional diversity among the mere handful of validated ncRNAs hints at the vast regulatory potential of these silent biomolecules.

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Shhh! Silencing by microRNA-155.

Philos Trans R Soc Lond B Biol Sci

March 2009

Small RNAs mediate a diverse pot-pourri of post-transcriptional silencing mechanisms, ranging from 'classical' RNA interference (RNAi), to gene repression by microRNAs (miRNAs), to maintenance of genomic stability by repeat-associated small RNAs. Here, we review recent findings on the function of miR-155, particularly its roles in mammalian innate and adaptive immunity, viral infection and oncogenesis.

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B lymphocytes perform somatic hypermutation and class-switch recombination (CSR) of the immunoglobulin locus to generate an antibody repertoire diverse in both affinity and function. These somatic diversification processes are catalyzed by activation-induced cytidine deaminase (AID), a potent DNA mutator whose expression and function are highly regulated. Here we show that AID was regulated posttranscriptionally by a lymphocyte-specific microRNA, miR-155.

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MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. In order to identify miRNAs and to assess their expression patterns, we sequenced over 250 small RNA libraries from 26 different organ systems and cell types of human and rodents that were enriched in neuronal as well as normal and malignant hematopoietic cells and tissues. We present expression profiles derived from clone count data and provide computational tools for their analysis.

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The immunoglobulin (Ig) repertoire achieves functional diversification through several somatic alterations of the Ig locus. One of these processes, somatic hypermutation (SHM), deposits point mutations into the variable region of the Ig gene to generate higher-affinity variants. Activation-induced cytidine deaminase (AID) converts cytidine to uridine to initiate the hypermutation process.

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Argonaute proteins associate with small RNAs that guide mRNA degradation, translational repression, or a combination of both. The human Argonaute family has eight members, four of which (Ago1 through Ago4) are closely related and coexpressed in many cell types. To understand the biological function of the different Ago proteins, we set out to determine if Ago1 through Ago4 are associated with miRNAs as well as RISC activity in human cell lines.

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In plants, animals and fungi, active centromeres are associated with arrays of repetitive DNA sequences. The outer repeats at fission yeast (Schizosaccharomyces pombe) centromeres are heterochromatic and are required for the assembly of an active centromere. Components of the RNA interference (RNAi) machinery process transcripts derived from these repeats and mediate the formation of silent chromatin.

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Eukaryotic heterochromatin is characterized by a high density of repeats and transposons, as well as by modified histones, and influences both gene expression and chromosome segregation. In the fission yeast Schizosaccharomyces pombe, we deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference (RNAi). Deletion results in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats.

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